Because of the known association of activated oncogenes with human lung cancers, the expected roles of these genes in the multiple steps leading to metastatic cancer and the possible linkage between phenotypic alterations and oncogene activation in carcinomas, it is important to define these relationships. The role of transfected oncogenes on normal human bronchial epithelial cells (NHBE) is being investigated using assays that measure transient alterations of expression of the differentiated phenotype. Cloned activated oncogenes are introduced into NHBE cells by strontium phosphate transfection. "Immortalization" or escape from senescence is evidenced by the appearance of transformed colonies. Since this process is lengthy, direct effects of exogenous genes may be difficult to detect. Therefore, the transient assay approach is used to assess direct effects of oncogenes in the short term. Preliminary results indicate that HVV-fos, a chimeric construct of human c-fos(human)-1 and a viral 3'long terminal repeat (LTR), induces serum resistance and extends the life span of NHBE cells. Use of the short-term assay will facilitate study of the action and interaction of activated oncogenes during multistage lung carcinogenesis and progression.